Maintenance of tissue homeostasis is dependent on the communication between stem cells and supporting cells in the same niche. Regulatory T cells (T_reg cells) are emerging as a critical component of the stem-cell niche for supporting their differentiation. How T_reg cells sense dynamic signals in this microenvironment and communicate with stem cells is mostly unknown. In the present study, by using hair follicles (HFs) to study T_reg cell–stem cell crosstalk, we show an unrecognized function of the steroid hormone glucocorticoid in instructing skin-resident T_reg cells to facilitate HF stem-cell (HFSC) activation and HF regeneration. Ablation of the glucocorticoid receptor (GR) in T_reg cells blocks hair regeneration without affecting immune homeostasis. Mechanistically, GR and Foxp3 cooperate in T_reg cells to induce transforming growth factor β3 (TGF-β3), which activates Smad2/3 in HFSCs and facilitates HFSC proliferation. The present study identifies crosstalk between T_reg cells and HFSCs mediated by the GR–TGF-β3 axis, highlighting a possible means of manipulating T_reg cells to support tissue regeneration.

组织稳态的维持依赖于同一生态位中干细胞和支持细胞之间的通讯。调节性 T 细胞（T _reg细胞）正在成为支持其分化的干细胞生态位的关键组成部分。 T _reg细胞如何感知这种微环境中的动态信号并与干细胞进行交流目前尚不清楚。在本研究中，通过使用毛囊 (HF) 研究 T _reg细胞与干细胞的串扰，我们发现类固醇激素糖皮质激素在指导皮肤驻留 T _reg细胞促进 HF 干细胞 (HFSC) 激活方面具有未被识别的功能和高频再生。 T _reg细胞中糖皮质激素受体 (GR) 的消融会阻止毛发再生，但不会影响免疫稳态。从机制上讲，GR 和 Foxp3 在 T _reg细胞中协同诱导转化生长因子 β3 (TGF-β3)，从而激活 HFSC 中的 Smad2/3 并促进 HFSC 增殖。本研究确定了 GR-TGF-β3 轴介导的 T _reg细胞和 HFSC 之间的串扰，强调了操纵 T _reg细胞支持组织再生的可能方法。